RT Journal Article
T1 GnRH replacement rescues cognition in Down syndrome.
A1 Manfredi-Lozano, Maria
A1 Leysen, Valerie
A1 Adamo, Michela
A1 Paiva, Isabel
A1 Rovera, Renaud
A1 Pignat, Jean-Michel
A1 Timzoura, Fatima Ezzahra
A1 Candlish, Michael
A1 Eddarkaoui, Sabiha
A1 Malone, Samuel A
A1 Silva, Mauro S B
A1 Trova, Sara
A1 Imbernon, Monica
A1 Decoster, Laurine
A1 Cotellessa, Ludovica
A1 Tena-Sempere, Manuel
A1 Claret, Marc
A1 Paoloni-Giacobino, Ariane
A1 Plassard, Damien
A1 Paccou, Emmanuelle
A1 Vionnet, Nathalie
A1 Acierno, James
A1 Maceski, Aleksandra Maleska
A1 Lutti, Antoine
A1 Pfrieger, Frank
A1 Rasika, S
A1 Santoni, Federico
A1 Boehm, Ulrich
A1 Ciofi, Philippe
A1 Buée, Luc
A1 Haddjeri, Nasser
A1 Boutillier, Anne-Laurence
A1 Kuhle, Jens
A1 Messina, Andrea
A1 Draganski, Bogdan
A1 Giacobini, Paolo
A1 Pitteloud, Nelly
A1 Prevot, Vincent
AB At the present time, no viable treatment exists for cognitive and olfactory deficits in Down syndrome (DS). We show in a DS model (Ts65Dn mice) that these progressive nonreproductive neurological symptoms closely parallel a postpubertal decrease in hypothalamic as well as extrahypothalamic expression of a master molecule that controls reproduction-gonadotropin-releasing hormone (GnRH)-and appear related to an imbalance in a microRNA-gene network known to regulate GnRH neuron maturation together with altered hippocampal synaptic transmission. Epigenetic, cellular, chemogenetic, and pharmacological interventions that restore physiological GnRH levels abolish olfactory and cognitive defects in Ts65Dn mice, whereas pulsatile GnRH therapy improves cognition and brain connectivity in adult DS patients. GnRH thus plays a crucial role in olfaction and cognition, and pulsatile GnRH therapy holds promise to improve cognitive deficits in DS.
YR 2022
FD 2022-09-02
LK http://hdl.handle.net/10668/20028
UL http://hdl.handle.net/10668/20028
LA en
DS RISalud
RD Apr 9, 2025